The invention relates generally to compounds with cell modifying activity and, in particular, to those with modifying activity also suitable under hypoxic conditions.
Current therapies directed against cells with uncontrolled growth properties (e.g., high proliferating cells, cancerous cells and tumors) require that they include a set of unique criteria in order to avoid damaging normal growing and/or nonproliferating cells. Such criteria include an ability to activate toxic compounds as well as a preferential action under low oxygen microenvironments in which most solid tumors exist. The latter is particularly important because it has been found that hypoxic subpopulations of cells exist in solid tumors that are directly linked with negative outcomes, such as a resistance to radiotherapy, resistance to a number of forms of chemotherapy, stimulation of metastasis, as examples.
Unfortunately, current therapies are generally lacking and few agents work better under hypoxic conditions than normal conditions. Accordingly, there remains a need for compounds with activity on biologic targets, especially compounds with activity under more hypoxic conditions. In addition, there remains a need for such compounds with suitable activity against targets, such as cells with uncontrolled growth properties, and with chemotherapeutic activity. A considerable therapeutic benefit would be achieved if such compounds were available, and could be combined with other treatments, to reduce or eliminate toxic portions of these biologic targets, such as cancerous cells and tumors.